The bombesin-like peptides are widely expressed in mammalian brain, gastrointestinal tract, normal lung, and cancerous lung. We have made the observation that bombesin-like peptides are also widely expressed in male and female reproductive tract and may play a role in modulating the acrosome reaction, and hence the fertilization of ovum by sperm. Two mammalian bombesin-like peptides have been characterized to date, GRP (gastrin-releasing peptide) and NMB (neuromedin B). Northern blot analysis shows that the GRP receptor is present in spermatocytes. We have shown that treatment of sperm with either GRP or bombesin with doses ranging from 2-100 nanomolar induces the acrosome reaction. The ability of bombesin to stimulate the acrosome reaction can be specifically blocked by GRP receptor antagonists. Preliminary studies have demonstrated that GRP receptor antagonists can also block the efficiency of in vitro fertilization of monkey oocytes. This suggests that GRP receptor antagonists could have contraceptive potential and that, conversely, GRP receptor agonists could enhance the efficiency of in vitro fertilization. Thus, we hypothesize that there is a regulatory pathway in which a bombesin-like peptide is released to modulate the acrosome reaction. The critical question becomes what is the source of this bombesin-like peptide is it present in the sperm, in the female reproductive tract, or both? To approach this question, we prepared a cDNA library from sperm and screened it with a GRP cDNA. Sequence analysis of hybridizing clones revealed that a new bombesin-like peptide was encoded by an alternate transcript of the GRP gene, a transcript that arose by use of an upstream initiation site and a new exon 1. We have named this new peptide ARP (acrosome-releasing peptide). ARP has been synthesized and shown to stimulate the acrosome reaction approximately as potently as GRP and bombesin. RNA blot analysis has also revealed that GRP and ARP are present in cervix and uterus. Thus, it is likely that there is both a male and female contribution to the role of bombesin-like peptides as modulators of the acrosome reaction. Current studies are focusing on the ability of GRP to increase the efficiency of fertilization of monkey oocytes by sperm.